Psychiatry Clin Neurosci. 2025 Feb 12. doi: 10.1111/pcn.13800. Online ahead of print.

ABSTRACT

AIM: Vafidemstat is a brain-penetrant, orally bioavailable, small molecule irreversible inhibitor of the histone lysine-specific demethylase KDM1A (also known as LSD1), which corrects memory deficits and behavior alterations including aggression and social interaction deficits in preclinical models.

METHODS: Here, we report the results of REIMAGINE, a phase IIa, single-center, open-label, one-arm basket trial that evaluated the safety and efficacy of vafidemstat on aggression in adult patients with borderline personality disorder (BPD), attention-deficit/hyperactivity disorder (ADHD), and autistic spectrum disorder (ASD). Participants received 1.2 mg/day of vafidemstat for 8 weeks.

RESULTS: Vafidemstat was shown to be safe and well tolerated, and no drug-related clinically significant adverse events were observed. Furthermore, all neuropsychiatric scales assessed showed notable efficacy signals, whether assessing agitation/aggression (Clinical Global Impression for Severity [CGI-S] and Clinical Global Impression for Improvement [CGI-I] and Neuropsychiatric Inventory [NPI] questionnaire for Agitation-Aggression [NPI-AA]), overall patient functioning (total NPI), or disease-specific features (Attention-Deficit/Hyperactivity Disorder Rating Scale [ADHD-RS] and Borderline Personality Disorder Checklist [BPDCL]). Statistically significant improvements were observed in the aggregated data (all participants) and for each of the three disease groups independently. Changes were evident within the first 2 weeks of treatment.

CONCLUSION: In summary, the REIMAGINE study supports that vafidemstat is safe, well tolerated, and causes a significant and consistent reduction in agitation/aggression and nonaggression features in BPD, ADHD, and ASD. These data support continuing the development of vafidemstat as a new treatment option for these psychiatric disorders.

PMID:39936839 | DOI:10.1111/pcn.13800

HIV Res Clin Pract. 2025 Dec;26(1):2456890. doi: 10.1080/25787489.2025.2456890. Epub 2025 Feb 12.

ABSTRACT

BACKGROUND: BICtegravir Single Tablet Regimen (BICSTaR) is an observational cohort study evaluating the effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in treatment-naïve (TN) and treatment-experienced (TE) people with HIV.

OBJECTIVE: To present final pooled 24-month outcomes for the full cohort.

METHODS: Prospective data were pooled from TN and TE adults with HIV initiating B/F/TAF in routine clinical practice across 14 countries (data collection: 25/06/2018-29/12/2023). Outcomes at 24 months included virologic suppression (HIV-1 RNA <50 copies/mL), immunologic effectiveness (change in CD4 cell count and CD4/CD8 ratio), persistence, and safety. Outcomes were also analysed in key populations.

RESULTS: Of 2,074 (483 TN, 1,591 TE) participants included, most were male (85%), White (70%), and had ≥1 comorbidity (66%). Median (Q1, Q3) age was 45 (35, 54) years. At 24 months, 94% of TN and 96% of TE participants had HIV-1 RNA <50 copies/mL (missing = excluded analysis). These values were 88% and 86%, respectively, in a discontinuation = failure analysis. Effectiveness remained high across all key populations at 24 months. Median (Q1, Q3) CD4 count increased by 257 (127, 447) cells/µL in TN and 40 (-70, 153) cells/µL in TE participants (both p < 0.001). There was no reported treatment-emergent resistance to B/F/TAF. Persistence was high at 24 months (TN, 95%; TE, 91%). Drug-related adverse events occurred in 11% of TN and 12% of TE participants, leading to B/F/TAF discontinuation in 5%.

CONCLUSIONS: B/F/TAF was generally well tolerated over 24 months, with high effectiveness and persistence observed among a broad range of people with HIV.

PMID:39936702 | DOI:10.1080/25787489.2025.2456890

Hum Vaccin Immunother. 2025 Dec;21(1):2465161. doi: 10.1080/21645515.2025.2465161. Epub 2025 Feb 12.

ABSTRACT

In light of the widespread use of rotavirus vaccines, there is a pressing need to perform thorough, large-scale surveillance to actively monitor safety. This study aimed to identify potential adverse events following rotavirus vaccination in infants. Using a nationwide linked database of the national immunization registry and health insurance claims data, we identified infants vaccinated with the first dose of rotavirus vaccine between January 2016 and October 2022. The self-controlled tree-temporal scan statistics method analyzed all incident diagnoses recorded within 56 days post-vaccination and evaluated all temporal risk windows. Among 1,720,778 rotavirus vaccine recipients 64,752 infants contributed to the analysis, yielding 72,970 incident diagnoses. Of these, 28 clusters were categorized as known adverse drug reactions (ADRs), including infection following immunization (Days 1-2, p<.001), viral infection (Days 1-5, p<.001), urticaria and erythema (Days 3-9, p<.001), acute upper respiratory infections (Days 28-42, p<.001), and pneumonia (Days 9-19 or 28-42, p<.001). Seventeen clusters were classified as ADR-related events, such as the ones clinically related to ADR or lower-level diagnostic codes of ADR. The remaining 26 clusters were classified as signals, including sepsis (Days 1-20, p<.001), meningitis (Days 1-23, p<.001), liver disease (Days 4-11, p<.001), and tubulo-interstitial nephritis (Days 11-38, p<.001). A cluster of intussusceptions was only found in monovalent vaccine-stratified analysis (Days 5-8, p = 0.005). This study confirmed known ADRs following rotavirus vaccination, while identifying potential safety signals requiring further investigation. These findings emphasize the importance of active vaccine surveillance and underscore the need for epidemiological studies with validated outcome definitions to confirm causal relationships between rotavirus vaccination and the detected outcomes.

PMID:39936376 | DOI:10.1080/21645515.2025.2465161

F1000Res. 2024 Jul 23;11:1388. doi: 10.12688/f1000research.125815.2. eCollection 2022.

ABSTRACT

Background Tuberculosis (TB) continues to pose a serious threat to the public health system in India. Although the National Tuberculosis Elimination Program (NTEP) is providing a wide range of interventions from early diagnosis to complete treatment to reduce morbidity and mortality from TB, adverse drug reactions (ADR) remain a challenge in treatment adherence and completion. Methods An observational cross-sectional study was conducted in selected districts of Gujarat state. A total of 593 reported TB patients were recruited with an adjusted unified distribution based on the type of cases, site of diseases, and service facility through a simple random sampling method. A semi-structured questionnaire tool was used to collect socio-demographic, clinical, and ADR-related data from the TB patients. Data was analyzed for the frequency, percentage, chi-squared, and adjusted odds ratio to find the association between the variables. Results The majority of the study participants were male (87.2%), aged 15 to 60 (57.8%), daily laborers (22.4%), and married (64.2%). Over 75% of individuals had pulmonary TB, with 87% having experienced their first episode, 83% being new cases, and 44.7% having a history of addiction. ADR with mild symptoms was reported by more than a quarter (29%) of TB patients during the intensive phase (77%). The association between ADR experience and drug susceptibility was significant (p<0.005) and drug-resistant TB patients experience two times more ADRs than drug-sensitive TB patients (OR 2.04). Binomial logistic regression was carried out to describe the association between various variables and occurrence of ADRs. Conclusion The study highlighted a need to enhance health care providers' capacity and program structure for managing ADRs among TB patients. In order to completely eliminate TB across the country, it also emphasized the attention for a holistic and all-encompassing strategy for managing TB patients at the field level.

PMID:39935535 | PMC:PMC11811607 | DOI:10.12688/f1000research.125815.2

BMC Nephrol. 2025 Feb 11;26(1):67. doi: 10.1186/s12882-025-04011-8.

ABSTRACT

BACKGROUND: Kidney dysfunction among adults living with Human Immuno-Deficiency Virus (HIV) increases the risk of drug-related side effects, acute kidney injury, hospitalization, and progression to end-stage kidney disease. In developing regions like Africa, where access to kidney transplants and dialysis is limited, early detection of kidney disease among adults living with HIV has significant clinical and financial implications. Therefore, the objective of this review was to determine the pooled prevalence and identify associated factors of kidney dysfunction among adults living with HIV in Africa.

METHODS: The report was presented according to the Preferred Reporting Items for Systematic Review and Meta-Analyses checklists. The articles were searched using PubMed/MEDLINE, EMBASE, Scopus, Wiley Online Library, CINAHL/EBSCO, OVID/Wolters Kluwer, Cochrane Library, Google Scholar, Science Direct, and African Journal Online. Data were extracted using Microsoft Excel and exported to STATA MP Version 11 Software for analysis. Heterogeneity of studies was assessed by Cochran's Q test and I2 statistics. Publication bias was detected by the visual inspection of the funnel plot and statistical Egger's test.

RESULTS: In this study, the pooled prevalence of kidney dysfunction among adults living with HIV in Africa is estimated to be 16.85% (95% CI: 13.08 - 20.62, I²=96.2%, p-value = 0.000). Female sex (POR = 1.82; 95% CI; 1.31, 2.53), age ≥ 50 years (POR = 8.94; 95% CI: 1.82, 43.93), body mass index ≥ 30 kg/m² (POR = 4.70; 95% CI: 3.07, 7.22), diabetes mellitus (POR = 2.84; 95% CI: 1.59, 5.07), CD4 count < 200 cells/mm³ (POR = 3.64; 95% CI: 1.63, 8.13) and anemia (POR = 3.73, 95% CI = 2.00-6.94) were factors associated with kidney dysfunction among adults living with HIV.

CONCLUSIONS: This study revealed that the pooled prevalence of kidney dysfunction among adults living with HIV in Africa remains significant. Female sex, age ≥ 50 years, body mass index ≥ 30 kg/m², diabetes mellitus, CD4 count < 200 cells/mm³ and anemia were factors associated with kidney dysfunction. To reduce the morbidity and mortality associated with kidney dysfunction, it is advisable to create awareness and initiating early interventions through health education during their follow-up time, and initiating suitable medication at an early stage.

PMID:39934651 | DOI:10.1186/s12882-025-04011-8

Dialogues Clin Neurosci. 2025 Dec;27(1):10-19. doi: 10.1080/19585969.2025.2463443. Epub 2025 Feb 11.

ABSTRACT

BACKGROUND: Psychotropic medications are critical in managing severe mental illnesses (SMI) such as schizophrenia, major depressive disorder (MDD) and bipolar disorder. However, these treatments often lead to adverse side effects that can impair patients' quality of life (QoL) and affect treatment adherence.

OBJECTIVE: This study aims to investigate the specific side effects of psychotropic treatments that contribute to a decline in QoL among patients with SMI, independently of treatment adherence.

METHODS: We conducted a cross-sectional study with 1248 patients diagnosed with SMI, recruited from a university psychiatric unit in Marseille, France. QoL was assessed using the Schizophrenia Quality of Life Scale (SQoL-18), and side effects were measured using the UKU Side Effect Rating Scale. Treatment adherence was evaluated using the Medication Adherence Rating Scale (MARS). Statistical analyses included Pearson correlations and multiple linear regression models to identify predictors of QoL.

RESULTS: The study found that side effects, as identified by the UKU scores, could significantly predict a reduction in QoL across multiple domains, including multiple dimensions of QoL and the overall QoL index, independent of treatment adherence. Patients on antipsychotics and benzodiazepines reported higher levels of adverse side effects, which correlated with lower QoL scores. An increase in the number of psychotropic treatment classes was also associated with a significant decline in QoL (p < 0.001).

CONCLUSION: Managing psychic side effects and minimising polypharmacy are critical to improving QoL in patients with SMI. Clinicians should consider these factors when developing personalised treatment strategies to enhance patient outcomes.

PMID:39933032 | DOI:10.1080/19585969.2025.2463443

Inflammopharmacology. 2025 Feb 11. doi: 10.1007/s10787-025-01647-8. Online ahead of print.

ABSTRACT

In the dynamic realm of scientific inquiry, the identification and characterization of biologically active compounds derived from plant extracts have become of utmost significance. A particularly noteworthy flavonoid in this regard is aromadendrin (AMD), which can be found in a diverse range of foods, fruits, plants, and natural sources. The versatility of this compound is evident through its wide array of biological properties, including its well-documented anti-inflammatory, antioxidant, antidiabetic, neuroprotective, immunomodulatory, cardioprotective, and hepatoprotective effects. These diverse actions validate its potential utilization in addressing drug-related side effects, adverse reactions, neoplasms, ulcers, jaundice, diabetes mellitus, dermatitis, neurodegenerative diseases, cognitive disorders, polyploidy, carcinomas, common colds, and cumulative trauma disorders. This review aims to unlock the full potential of AMD and pave the way for groundbreaking advancements in the fields of medicine and nutrition. Prepare to embark on an enthralling journey as we unveil the hidden treasures and extraordinary prospects associated with AMD.

PMID:39932620 | DOI:10.1007/s10787-025-01647-8

Curr Drug Saf. 2025 Feb 7. doi: 10.2174/0115748863356840250112181406. Online ahead of print.

ABSTRACT

Pharmacovigilance is an important subject in medicine and healthcare, which aims to prevent side effects and other drug-related problems by identifying, evaluating, understanding, and avoiding them. Its main objectives are ensuring that a drug's benefits balance its hazards and improving patient safety. Within medicine and healthcare, pharmacovigilance is an essential subject that focuses on identifying, evaluating, comprehending, and preventing side effects or any other issues associated with drugs. Its main objective is to improve patient safety and ensure a drug's advantages exceed its drawbacks. Pharmacovigilance has evolved significantly as a result of technological advancements, enabling more efficient medication, safety monitoring, and management. The combination of machine learning (ML) with artificial intelligence (AI) for data analysis, adverse reaction prediction, and signal detection, electronic health records (EHRs), and mobile health (mHealth) applications have enhanced real-time data collecting and expedited the reporting of adverse drug reactions (ADRs). Pharmacovigilance plays an important role which focuses on detecting, assessing, comprehending, and averting adverse medication reactions. Making sure a drug's advantages outweigh its disadvantages is its main objective to improve patient safety. Pharmacovigilance, which balances patient safety, efficacy, and regulatory compliance in clinical trials, is necessary to promote the safe and effective use of drugs.

PMID:39931995 | DOI:10.2174/0115748863356840250112181406

Mol Pharm. 2025 Feb 11. doi: 10.1021/acs.molpharmaceut.4c01197. Online ahead of print.

ABSTRACT

Alcohol liver disease (ALD) is a chronic liver disorder resulting from long-term heavy alcohol consumption. The pathogenesis of ALD is multifactorial, and existing therapeutic agents primarily target specific aspects of the disease while presenting significant side effects, including drug-induced liver injury and hepatobiliary disease. Silibinin (SLB) has attracted widespread attention for its hepatoprotective effects and favorable safety profile. However, inherent limitations associated with SLB, such as poor solubility and bioavailability, have significantly limited its clinical application. Drug delivery systems, including liposomes, offer promising potential for the delivery of hydrophobic drugs. However, the selection of an appropriate delivery vehicle requires optimization. Ursodeoxycholic acid sodium (UAS) serves as a promising alternative to cholesterol in liposomal formulations, offering a potential strategy to mitigate the health risks associated with cholesterol. In this study, UAS was employed as the liposomal membrane material to prepare a UAS liposome loaded with SLB (SUL), and its efficacy and mechanism of action in alcoholic-induced liver injury were subsequently evaluated. The experimental results demonstrated that SUL exhibited a uniform particle size distribution, good stability, and an effective release profile in vitro. Following oral administration, SUL effectively inhibited alcohol-induced liver damage, oxidative stress, and fat accumulation. In addition, SUL regulated the expression of the kelch-1ike ECH- associated protein l (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) proteins, thereby exerting antioxidative stress effects. Furthermore, it also modulated apoptosis-related factors, including B-cell lymphoma-2 (Bcl-2), BCL-2-associated X (Bax), cysteinyl aspartate specific proteinase-3 (Caspase-3), and cleaved caspase-3, to mitigate hepatocyte apoptosis. In summary, SUL demonstrates enhanced therapeutic efficacy against ALD, offering a novel approach for the clinical application of SLB in the prevention and treatment of ALD.

PMID:39931930 | DOI:10.1021/acs.molpharmaceut.4c01197

Orphanet J Rare Dis. 2025 Feb 10;20(1):64. doi: 10.1186/s13023-025-03564-z.

ABSTRACT

BACKGROUND: In patients with slow-flow vascular malformations (SFVMs) including venous malformations (VM), lymphatic malformations (LM) or Klippel-Trenaunay Syndrome (KTS), somatic gain-of-function mutations in genes encoding phosphatidyl inositol 3-kinase alpha (PI3Kα, gene name PIK3CA) have been identified. A phase 2 study was conducted with the patients to assess the efficacy and safety of ART-001 (serabelisib), an orally available selective PI3Kα inhibitor.

METHODS: This is a multicenter, randomized, double-blind, proof-of-concept, phase 2 trial. Eligible participants were patients aged 2 years and older, diagnosed either with VM, LM or KTS. Participants were administered either 50 or 100 mg of ART-001 for 24 weeks. The primary endpoint was the response rate defined as the proportion of participants who achieved ≥ 20% reduction in lesion volume at week 24. Secondary endpoints include safety, pharmacokinetics, pain, and quality of life scores.

RESULTS: Thirty-five patients (median age: 14 years old; VM, n = 17, KTS, n = 13 and LM, n = 5) were randomly assigned and received treatment (50 mg, n = 17 and 100 mg, n = 18). ART-001 showed a response rate: 29.4% (95% confidence interval 10.3-56.0%) at 50 mg and 33.3% (13.3-59.0%) at 100 mg. Mean lesion volume reductions at 50 mg and 100 mg were - 2.3% (95% CI - 14.3 to 9.6%) and - 12.6% (- 25.3 to 0.06%), respectively. No drug-related serious adverse events were observed. Treatment-emergent adverse events were generally mild to moderate and transient. Pharmacokinetic profiles were similar between pediatric and adolescent/adult patients except for lower Ctrough levels in pediatric patients.

CONCLUSION: ART-001 was effective and well-tolerated in patients with SFVMs. These results support the further development of ART-001 in SFVMs and other PIK3CA-related overgrowth syndromes to confirm clinical benefits and long-term safety.

TRIAL REGISTRATION: Japan Registry of Clinical Trial, jRCT2071210027. Registered May 25 2021, https://jrct.niph.go.jp/en-latest-detail/jRCT2071210027.

PMID:39930502 | DOI:10.1186/s13023-025-03564-z

Virol J. 2025 Feb 10;22(1):33. doi: 10.1186/s12985-025-02648-3.

ABSTRACT

BACKGROUND: There are limited data on how historical nucleoside reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs) other than M184V/I, affect the activity of B/F/TAF. We evaluated the outcomes of switching virologically suppressed (HIV-1 RNA < 50 copies/mL) individuals harbouring major RAMs from boosted protease inhibitor (bPI)-based therapy to B/F/TAF.

METHODS: Participants had various historical genotypic patterns including M184V/I, ≤2 thymidine analogue mutations (TAMs), and other NRTI RAMs (NAMs), and no integrase resistance. Baseline RAMs were explored by retrospective sequencing of cellular HIV-1 DNA. Participants were randomised (1:1) to switching to B/F/TAF either immediately or after 24 weeks. The primary outcome was the proportion of participants maintaining virological suppression (pure virologic response) at week-24; secondary outcomes were proportion of participants with virological suppression at week-48, pre-specified safety measures, and treatment-emergent resistance.

RESULTS: Historically, 21/72 (29.2%) participants had M184V/I, 5 (6.9%) M184V/I + 1 NAM, 31 (43.1%) 1 TAM ± M184V/I ± 1 NAM, and 15 (20.8%) 2 TAMs ± M184V/I ± 1 NAM. At week-24, proportions maintaining virological suppression were 33/33 (100%) on B/F/TAF vs. 38/39 (97.4%) on bPI (difference 2.6%; 95% CI -2.4%, 7.5%). Drug-related adverse events (AEs) were reported in 10/33 (30.3%) vs. 1/39 (2.6%), respectively. The immediate switch arm had improved lipid parameters but increased HbA1c and weight. Virological suppression was maintained at week-48. There were six discontinuations; four on B/F/TAF were drug-related and the two on bPI were not drug-related.

CONCLUSIONS: Historical NRTI resistance did not compromise the effectiveness of B/F/TAF in virologically suppressed adults. 12% experienced treatment-limiting AEs after switching.

REGISTRATION: EudraCT no: 2018-004732-30.

PMID:39930490 | DOI:10.1186/s12985-025-02648-3

Arch Dermatol Res. 2025 Feb 11;317(1):383. doi: 10.1007/s00403-025-03925-5.

ABSTRACT

IgA vasculitis (IgAV) is a small-vessel vasculitis characterized by the deposition of immunoglobulin A (IgA) in the vessel walls, often presenting with cutaneous manifestations such as palpable purpura. Drug-induced IgAV is a rare but potentially severe condition. Several studies have suggested a possible association between antibiotics and IgAV. However, research on this link remains limited. This study aimed to identify antibiotics implicated in the onset of IgAV and to analyze the clinical characteristics of IgAV induced by antibiotics. Data on antibiotic-induced IgAV events were extracted from the FDA Adverse Event Reporting System (FAERS) database, and case reports were collected through literature searches. A pharmacovigilance analysis was conducted using FAERS data from 2003 to 2023 to evaluate adverse events related to IgAV caused by antibiotics, and case reports up to November 23, 2024, were reviewed for retrospective analysis. A total of 150 reports of antibiotic-induced IgAV were analyzed, with 13 antibiotics identified as associated with IgAV. The three antibiotics most strongly linked to IgAV were ofloxacin, vancomycin, and clarithromycin based on the FAERS database analysis. The median age of the cases was 58 years, with a male predominance. IgAV typically developed 4 days (1-15 days) after drug administration. Clarithromycin, vancomycin, and ciprofloxacin were the most frequently reported antibiotics in the literature, and they were also associated with poor renal outcomes, emphasizing the importance of regular follow-up to improve long-term renal prognosis. In conclusion, this study identified 13 antibiotics associated with IgAV, with ofloxacin, vancomycin, and clarithromycin being the most strongly linked to the condition.

PMID:39930301 | DOI:10.1007/s00403-025-03925-5

Zhongguo Zhong Yao Za Zhi. 2025 Jan;50(1):273-277. doi: 10.19540/j.cnki.cjcmm.20240905.601.

ABSTRACT

Signal detection is a critical task in drug safety regulation. However, it inevitably generates irrelevant or false signals, posing challenges for resource allocation by marketing authorization holders. To reasonably assess these signals, different countries have established various principles for prioritizing the evaluation of risk signals. This study systematically compares these principles and finds that the U.S. Food and Drug Administration(FDA) focuses on practical issues, such as identifying drug confusion or drug interactions. However, China's Good Pharmacovigilance Practices and the European Medicines Agency(EMA) emphasize a comprehensive evaluation framework. The Council for International Organizations of Medical Sciences(CIOMS) emphasizes the consistency of multiple data sources, highlighting the reliability of signal evaluation. China practices a multidisciplinary approach combining traditional Chinese and western medicine, and the risk signals related to traditional Chinese medicine(TCM) have unique characteristics, including complex components, cumulative toxicity, specific theoretical foundations, and drug interactions. The different priorities in risk signal evaluation principles across countries suggest that China should strengthen clinical trial research, emphasize corroboration with evidence of multiple sources, and pay particular attention to the risks of drug interactions in the TCM regulatory science. Establishing the risk signal prioritization principles that align with the characteristics of TCM enables more precise and efficient scientific regulation of TCM.

PMID:39929668 | DOI:10.19540/j.cnki.cjcmm.20240905.601

Reg Anesth Pain Med. 2025 Feb 10:rapm-2025-106481. doi: 10.1136/rapm-2025-106481. Online ahead of print.

NO ABSTRACT

PMID:39929637 | DOI:10.1136/rapm-2025-106481

PLoS One. 2025 Feb 10;20(2):e0318139. doi: 10.1371/journal.pone.0318139. eCollection 2025.

ABSTRACT

BACKGROUND: Public involvement in reporting adverse drug reactions (ADRs) generates a broader database on drug safety. Underreporting remains a hindrance to implementing an effective pharmacovigilance system that ultimately affects public health. Hence, it is critical to appraise the public's awareness of ADR reporting and pharmacovigilance to address the gaps for the enhancement of ADR reporting rate.

OBJECTIVES: The current study explored public knowledge and attitudes toward ADR reporting in Karachi, Pakistan.

METHODS: A quantitative cross-sectional study was conducted from 3rd Jan 2022 to 30th Nov 2022 using a forty-item questionnaire to evaluate public insights regarding the ADR and its reporting. Descriptive analysis was executed to determine frequencies and percentages for the respondents' baseline characteristics and the responses toward ADR reporting. The chi-square test (χ2) was applied to determine the association between the dependent and independent variables considering a p-value < 0.05 as statistically significant.

RESULTS: The response rate of the present study was 78.3%. More than 80% of the respondents deemed that ADR occurs only with high doses of medicines and over-the-counter medications do not cause any ADR. More than 75% of the respondents did not know that the ADR reporting form is available on the Drug Regulatory Authority of Pakistan (DRAP) website; the response varied significantly with the education (p = 0.002) and social status (p = 0.0001) of the respondents. More than 50% of the participants refused to ever report an ADR to health professionals. Physicians (n = 364; 47.7%) and pharmacists (n = 253; 33.1%) were the respondents' professed most reliable sources to whom ADR can be reported; responses varied significantly with their education (p = 0.003) and age (p = 0.001).

CONCLUSIONS: The study has provided insight into the challenges and gaps needed to improve ADR reporting in Pakistan. The outcomes revealed that the public is aware of the benefits of reporting ADRs; however, they do not realize their role and the potentially significant impact on the healthcare system by contributing to ADR reporting. Therefore, it is a need of time to educate the public on the value of reporting ADRs and implement user-friendly and accessible ADR reporting systems in patient care areas to facilitate easier reporting.

PMID:39928620 | DOI:10.1371/journal.pone.0318139

Trials. 2025 Feb 9;26(1):46. doi: 10.1186/s13063-025-08723-y.

ABSTRACT

Adverse event (AE) collection is a key part of evidence generation in clinical trials and an integral element of safety reporting. AE assessment and documentation is particularly challenging in neonates who are a heterogeneous population with high rates of co-morbidities. Neonatal research is finally gaining the attention of regulators regarding drug development and the need for optimal dosing specific to this population. However, further efforts are necessary to ensure that adverse events (AEs) are adequately collected, allowing for the generation of essential safety data. It is also crucial that the methodology used aligns with the intended trial outcomes to minimise the burden on trial sites. In resource-constrained settings, where pharmacovigilance implementation can be particularly challenging, a pragmatic approach to safety reporting is even more important given the significant public health need for effective drugs. This commentary reflects on some of the challenges and potential areas of improvement in safety reporting that could be addressed in future neonatal-focused trials.

PMID:39924475 | DOI:10.1186/s13063-025-08723-y

Sci Rep. 2025 Feb 8;15(1):4783. doi: 10.1038/s41598-025-89272-x.

ABSTRACT

This study aims to identify and evaluate the most common drugs associated with the risks of autoimmune hepatitis (AIH) using the FDA Adverse Event Reporting System (FAERS) database. Adverse drug events (ADEs) associated with drug-induced AIH (DI-AIH) were retrieved from the FAERS database (January 2004-June 2024). Disproportionality analysis was performed to identify drugs significantly linked to DI-AIH, and time-to-onset (TTO) analyses were conducted to evaluate the timing and risk profiles of DI-AIH adverse reactions. Our study identified 2,511 ADEs linked to autoimmune hepatitis. Disproportionality analysis identified 22 drugs significantly associated with AIH risk, including 4 antibiotics, 3 antivirals, 4 cardiovascular drugs, 5 antitumor agents, 2 immunomodulators, 2 nonsteroidal anti-inflammatory drugs, and 1 drug each from the respiratory and nervous system categories. The highest DI-AIH risks were observed with minocycline (ROR = 53.97), nitrofurantoin (ROR = 57.02), and doxycycline (ROR = 16.12). Antitumor drugs had the shortest median TTO (77.00 days), whereas cardiovascular drugs exhibited the longest (668.30 days). Through a comprehensive analysis of the FAERS database, our study identified drugs strongly associated with AIH. Preventing DI-AIH requires careful drug selection and monitoring. This study provides evidence-based insights into implicated drugs, aiming to optimize clinical management and mitigate risks.

PMID:39922875 | DOI:10.1038/s41598-025-89272-x

Eur J Hosp Pharm. 2025 Feb 8:ejhpharm-2024-004352. doi: 10.1136/ejhpharm-2024-004352. Online ahead of print.

ABSTRACT

OBJECTIVES: This study addressed the gaps in the disclosure of statin-associated adverse drug reactions (ADRs) in China's official database and the inadequacy of cases reported relative to the population size in public ADR databases.

METHODS: To address these limitations, we conducted a retrospective trial-based analysis using data from Chinese journals to comprehensively assess statin-associated ADRs from 1992 to 2023, focusing on liver (2895 studies, n = 163 810) and muscle (2888 studies, n = 161 714) related outcomes.

RESULTS: For large sample size clinical trial analysis (n≥100), our analysis encompassed data from 31 763 participants for muscle-related ADRs (incidence rate: 0.004-0.006, common effect model; 0.002-0.006, random effects model) and 31 281 participants for liver-related ADRs (incidence rate: 0.004-0.006, common effect model; 0.003-0.006, random effects model), covering various statins, including atorvastatin, simvastatin, rosuvastatin, fluvastatin, pitavastatin, pravastatin and lovastatin. Notably, muscle-related ADRs, particularly rhabdomyolysis, were most prevalent with fluvastatin, lovastatin and pravastatin, showing rates of 0.90%, 0.74% and 0.53%, respectively. Pitavastatin and atorvastatin were frequently associated with liver-related ADRs such as abnormal liver function and elevated enzymes, with rates of 5.36% and 1.819%, respectively.

CONCLUSIONS: This study underscores significant variations in ADR incidence among different statins in the Chinese population, providing critical insights for healthcare professionals and policymakers to enhance patient safety and optimise clinical decisions regarding statin therapy.

PMID:39922684 | DOI:10.1136/ejhpharm-2024-004352

Indian J Gastroenterol. 2025 Feb 8. doi: 10.1007/s12664-024-01720-0. Online ahead of print.

ABSTRACT

BACKGROUND: This systematic review and meta-analysis evaluated the incidence of serious adverse events (SAEs) in patients with Crohn's disease (CD) and ulcerative colitis (UC) treated with upadacitinib and examined secondary adverse events.

METHODS: A comprehensive search of PubMed, Embase and Cochrane Library was conducted to identify randomized controlled trials (RCTs) comparing upadacitinib with placebo in adults with inflammatory bowel disease (IBD). The primary outcome was the incidence of SAEs, while secondary outcomes included specific adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were calculated.

RESULTS: Six RCTs, including 2611 patients, were analyzed. The incidence of SAEs did not significantly differ between upadacitinib (6.1%) and placebo (7%) (RR = 0.77; 95% CI: 0.50-1.20; p = 0.25). Secondary outcomes showed no significant differences in serious infections, hepatic disorders, nasopharyngitis or herpes zoster. However, neutropenia (RR = 5.63; 95% CI: 1.90-16.65; p = 0.0002) and creatine kinase elevation (RR = 2.34; 95% CI: 1.22-4.47; p = 0.01) were higher with upadacitinib, while anemia (RR = 0.36; 95% CI: 0.27-0.48; p < 0.00001) and arthralgia (RR = 0.47; 95% CI: 0.30-0.75; p = 0.001) were reduced.

CONCLUSION: Upadacitinib did not increase the overall risk of SAEs in IBD patients, with a notable reduction in anemia and arthralgia. However, the higher risks of neutropenia and CK elevation underscore the importance of monitoring. Further research is necessary to assess long-term safety, particularly regarding rare but serious events such as thromboembolism.

PMID:39921836 | DOI:10.1007/s12664-024-01720-0

J Thromb Haemost. 2025 Feb 5:S1538-7836(25)00050-9. doi: 10.1016/j.jtha.2025.01.008. Online ahead of print.

ABSTRACT

BACKGROUND: Andexanet alfa, a Food and Drug Administration (FDA)-approved antidote for apixaban and rivaroxaban, is used to manage life-threatening or uncontrolled bleeding. In patients undergoing cardiopulmonary bypass (CPB), prior exposure to andexanet can cause severe heparin resistance, necessitating effective mitigation strategies. A comprehensive review of such strategies remains lacking.

OBJECTIVE: To systematically review and characterize cases of andexanet-induced heparin resistance in patients undergoing CPB and to evaluate management strategies.

METHODS: A systematic search was conducted across multiple databases via the Ovid interface, Cochrane Central Register of Controlled Trials, and the FDA Adverse Event Reporting System. Quality appraisal was performed using a validated instrument for case reports and series describing drug-induced adverse events.

RESULTS: Fourteen discrete patient cases met inclusion criteria. Post-andexanet administration, the mean initial activated clotting time (ACT) was 199.5 seconds, falling short of a target of >400 seconds despite additional heparin dosing (mean total: 1,123 U/kg). 35.7% of all cases involved thrombus formation in the reservoir; two of which required a circuit replacement. Antithrombin (AT) concentrate was administered to 75% of those received an adjunct therapy. A prophylactic AT use (mean, 49.9 IU/kg) resulted in an ACT over 400 seconds, while its effects in low-dose after the occurrence of thrombosis varied on ACT values. Nafamostat mesylate was used in some cases reported from Japan CONCLUSIONS: Heparin resistance following andexanet exposure poses significant procoagulant risk during CPB. Preemptive high-dose antithrombin therapy may improve ACT values. Further studies are needed to understand the mechanisms and optimize management of this condition.

PMID:39920998 | DOI:10.1016/j.jtha.2025.01.008